Donor-specific anti-HLA antibodies in pediatric renal transplant recipients with creeping creatinine: Prevalence, histological correlations, and impact on patient and graft survival.

Donor-specific anti-HLA antibodies (DSA) causing CAMR are responsible for a high proportion of long-term graft failures after RTX. We studied the prevalence of DSA in RTX children biopsied for creeping Cr, its relationship with NA, and patient and graft survival according to histopathology. Between 2008 and 2013, 92 children were biopsied at a median of 38 months post-RTX. At biopsy, the prevalence of DSA was 49% and C4d 70%. NA rate was 45%, higher in adolescents (60%). Most frequent diagnoses were CAMR (72%) and interstitial fibrosis with tubular atrophy (IFTA) (28%). Forty-five of 66 patients with CAMR (68%) had detectable DSA. Twenty-one DSA-negative patients with CAMR had histological damage (IFTA + C4d positivity). C4d was detected in 64 of 66 biopsies with CAMR. Recipients with IFTA alone had neither C4d, nor detectable DSA, and were adherent. Graft survival at five yr was 89% in patients with CAMR, 79% in those with CAMR + TCMR Banff I, 33% in those with CAMR + TCMR Banff II, and 96% in those with IFTA. ABMR and complement activation were frequent in children biopsied for creeping Cr. Recipients with DSA were more likely to be non-adherent and have CAMR or CAMR + TCMR and worse graft survival.

Tratamiento con vincristina de tres tumores vasculares con fenómeno de Kasabach-Merritt / Vincristine treatment of three vascular tumors with Kasabach-Merritt phenomenon

El fenómeno de Kasabach-Merrit (FKM) es una coagulopatía por consumo que se presenta en las primeras semanas de la vida. Se caracteriza por presentar coagulopatía por consumo, con trombocitopenia y anemia hemolítica microangiopática, asociado a un tumor vascular. El objetivo de este trabajo es presentar tres pacientes con tumores vasculares que manifestaron FKM y fueron tratados con vincristina como droga de segunda línea, atendidos en el Servicio de Dermatología del Hospital de Pediatría J. P. Garrahan. Dos pacientes presentaron el tumor al nacimiento y otro a partir de los dos meses de vida. Dos fueron niñas y uno varón.Todos los pacientes tenían una trombocitopenia severa (3 000/mm_), bajos niveles de fibrinógeno y dimero D elevado. Los tumores estaban localizados en región proximal de miembro inferior, tronco y miembro superior, y región cervical. Ninguno de nuestros pacientes tuvo compromiso de órganos internos. El diagnóstico histológico en dos de ellos fue de hemangioendotelioma kaposiforme (HEK). Los corticoides fueron el tratamiento de primera linea: metilprednisona 3mg/kg/día por vía oral. En un paciente el tumor continuó creciendo a pesar de haber asociado interferón alfa 2 a la corticoterapia y realizarle secundariamente una embolización. Dada la falta de respuesta clínica y hematológica, se decidió iniciar tratamiento con vincristina 1mg/m2/dosis/IV semanal. Todos los pacientes normalizaron los parámetros hematológicos, con franca mejoría clínica, dos pacientes a la quinta y otro a la sexta dosis de vincristina, con involución gradual del tamaño del tumor. Ninguno de los pacientes presentó complicaciones secundarias al tratamiento ni recidivas de su enfermedad a la fecha. La duración promedio de tratamiento fue de 35±6 días. Podemos concluir que el uso de vincristina es considerado en la actualidad una droga de segunda línea en el tratamiento de tumores vasculares con FKM (AU)

Kasabach-Merritt phenomenon (KMP) is a consumptive coagulopathy that typicallly presents in the first few weeks of life. It is characterized by a triad of vascular tumor, thrombocytopenia and coagulopathy. We reviewed the clinical and hematologic data and response to therapeutic with vincristine in three patients who had a vascular tumor and KMP at the Dermatology Department of Hospital de Pediatría J. P. Garrahan.Tumors were present at birth in two patients and in one at two months old. Two were girls and one was a boy. All patients had severe thrombocytopenia (Lowest platelets count 3 000/mm_), consumption of fibrinogen and lower D-dimer levels.Tumors were localized on proximal lower limb, trunk and upper limb and cervical area. None of our patients had internal involvement. Histopathology finding in two of them was kaposiform hemangioendothelioma. First line of treatment was prednisolone 3-5mg/kg/day. In one patient the tumor size continued to increase in spite of simultaneous treatment with corticosteroid and interferon alfa-2a plus embolization. After corticosteroids treatment failure, correction of coagulopathy and tumor regression occurred in our three patients after 5 to 6 doses of vincristine 0.5-1mg/m_ IV weekly with almost complete tumor regression and correction of coagulopathy.The average duration of treatment was 35±6days. None of the patients developed complications due to this intervention nor experienced recurrence of the tumor.The use of vincristine is currently a second line treatment of vascular tumors with KMP (AU)

Isolated pulmonary Langerhans cell histiocytosis presenting with recurrent pneumothorax.

We describe the outcome of a 20-month-old female and a 6-year-old male, both of whom had acutely developed severe respiratory distress with tachypnea, cyanosis and, in Patient 2, thoracic pain. Chest X-ray and CT scan showed interstitial pulmonary involvement and a bullous process with bilateral pneumothoraces for both children. Pulmonary biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH). Laboratory testing and skeletal radiography did not reveal any other involvement of LCH. The patients received chemotherapy (prednisone, vinblastine, 6-mercaptopurine). They had recurrent episodes of pneumothorax during follow-up and placement of chest tubes was the treatment chosen. They were asymptomatic, with regression of bullae and disappearance of pneumothorax at 58 and 63 months of follow-up, respectively. Pulmonary function tests done during follow-up were normal in both patients. Despite severe pulmonary involvement, conservative surgical treatment and moderate chemotherapy produced good results in these two rare cases.

Reproducibility of the Banff classification in subclinical kidney transplant rejection.

The Banff classification for kidney allograft pathology has proved to be reproducible, but its inter and intraobserver agreement can vary substantially among centres. The aim of this study was to evaluate Banff reproducibility of surveillance renal allograft biopsies among renal pathologists from different transplant centres. This study included 32 renal transplant patients with stable graft function. Biopsies were performed 2 and 12 months post-transplant. Histology was interpreted according to the Banff schema by three renal pathologists, and inter and intraobserver agreement were measured. The best reproducibility was obtained for the presence or absence of acute rejection (AR), with kappa values ranging from moderate (kappa = 0.47; p = 0.006) to good (kappa = 0.72; p = 0.0001). However, the agreement for 'suspicious for AR' category was poor between all observers. For scoring and grading interstitial inflammation and intimal arteritis the agreement were poor and moderate, respectively. Reproducibility for the presence or absence of chronic allograft nephropathy (CAN) was heterogeneous, ranging from poor (kappa = 0.13; p = NS) to moderate (kappa = 0.56; p = 0.007). Scoring chronic changes such as fibrous intimal thickening gave a reasonable interobserver agreement. Intraobserver reproducibility was good for presence or absence of AR, but was poor for the diagnosis of CAN. In conclusion, histologic analysis of stable renal allografts based on Banff criteria showed a good agreement for the diagnosis of AR and a reasonable kappa for CAN, but reproducibility for scoring and grading showed a substantial interobserver variation.

Outcome in children with pulmonary Langerhans cell Histiocytosis.

BACKGROUND: The aim of this study was to evaluate features and outcome of children with Langerhans cell Histiocytosis (LCH) and pulmonary involvement. PROCEDURE: Retrospective evaluation of LCH patients was performed from 1987 to 2001. Multisystem patients were classified according to the pattern of organ system involvement into Groups: A (no pulmonary, hematologic, or hepatic involvement), B (pulmonary involvement), C (pulmonary and hematologic or hepatic involvement), and D (hematologic or hepatic involvement). All had skin, bone, or lymph node involvement. Chest X-ray was performed in all patients and computed tomography (CT) in 21. Diagnostic lung biopsy was performed in five patients. RESULTS: Pulmonary involvement was found in 36/220 patients studied. Two patients had isolated pulmonary involvement. Multisystem involvement was present in 83 patients, 34 of whom had pulmonary involvement. In 20/36 patients, tachypnea, cough, and thoracic pain occurred. Diffuse interstitial involvement was found in all cases. Pulmonary function tests were performed in nine patients, six of whom revealed mild to moderate restrictive respiratory involvement. The two patients having isolated pulmonary involvement survived 2 and 2.7 years after diagnosis. Median follow-up of all multisystem patients was 2.1 years, with a 5-year survival probability of 0.59. The 5-year survival probability of Groups A-D was 0.94, 0.83, 0.23, and 0.40, respectively. The survival difference between Groups B and C was statistically different (P < 0.0071). CONCLUSIONS: According to our data, pulmonary compromise without other risk organ involvement does not appear to be a negative prognostic factor in our study.

Prevalence and immunohistochemical findings of subclinical kidney allograft rejection and its association with graft outcome.

Subclinical acute rejection (SAR) occurs in about 30% of stable renal transplant patients and may be a risk factor for a poor allograft outcome. In the present study, the prevalence and clinical features of subclinical rejection, and the expression of immune activation markers in surveillance graft biopsies were assessed and correlated with late graft outcomes. Protocol biopsies were obtained at 2 and 12 months post-transplant in 32 and 26 patients, respectively, with stable renal function. The Banff 1997 criteria were used for histological diagnosis. Graft function and survival and proteinuria were assessed during the 36 months of follow-up. Immunohistochemical evaluation of cell subpopulations and immunoactivation markers were performed on protocol biopsies. The prevalence of SAR at 2 months and of chronic allograft nephropathy (CAN) at 12 months in representative biopsies was 55 and 50%, respectively. Patients with SAR presented mononuclear cell infiltration with an increased expression of CD3, CD4, CD68, IL-2R and granzyme B. Kidney graft function was significantly worse in patients with SAR at 2 months who had chronic rejection on biopsy at 12 months, but SAR was not associated with a worse graft function, greater proteinuria or a lower graft survival in 3 yr of follow-up. In conclusion, we found an elevated prevalence of SAR at 2 months after transplantation with an increased expression of activation markers. Although an association of SAR with poor graft outcome was not observed, our results suggest that SAR is an immunologically active process and underscore the importance of protocol biopsies in the surveillance of transplanted kidneys.

Lupus eritematoso neonatal: presentación de un caso y revisión de la literatura / Neonatal lupus: case report and literature review

El lupus eritematoso neonatal es un síndrome muy poco frecuente caracterizado por alteraciones cutáneas semejantes al lupus subagudo o discoide, acompañado frecuentemente por alteraciones cardíacas, en especial trastornos de la conducción, y alteraciones sistémicas. Se debe al pasaje pasivo transplacentario de anticuerpos antiRo y antiLa de la madre, quien padece o padecerá enfermedades relacionadas como lupus eritematoso sistémico, síndrome de Sjogren u otras enfermedades reumáticas. Presentamos el primer caso argentino conocido, en un lactante varón cuya madre y abuela materna padecían lupus eritematoso sistémico. Sus manifestaciones cutáneas, conformadas por máculo-pápulas eritematosas figuradas de cara y miembros y petequias en tronco, fueron desvaneciéndose con el correr de los meses. El niño se encontraba libre de lesiones cutáneas a los 6 meses de vida. La microscopía óptica y la inmunofluorescencia directa confirmaron el diagnóstico, siendo negativos los estudios de anticuerpos circulantes antiRo, antiLa, antiADN y antiRNP y positivo débil el FAN

Lupus eritematoso neonatal: presentación de un caso y revisión de la literatura / Neonatal lupus: case report and literature review

El lupus eritematoso neonatal es un síndrome muy poco frecuente caracterizado por alteraciones cutáneas semejantes al lupus subagudo o discoide, acompañado frecuentemente por alteraciones cardíacas, en especial trastornos de la conducción, y alteraciones sistémicas. Se debe al pasaje pasivo transplacentario de anticuerpos antiRo y antiLa de la madre, quien padece o padecerá enfermedades relacionadas como lupus eritematoso sistémico, síndrome de Sjogren u otras enfermedades reumáticas. Presentamos el primer caso argentino conocido, en un lactante varón cuya madre y abuela materna padecían lupus eritematoso sistémico. Sus manifestaciones cutáneas, conformadas por máculo-pápulas eritematosas figuradas de cara y miembros y petequias en tronco, fueron desvaneciéndose con el correr de los meses. El niño se encontraba libre de lesiones cutáneas a los 6 meses de vida. La microscopía óptica y la inmunofluorescencia directa confirmaron el diagnóstico, siendo negativos los estudios de anticuerpos circulantes antiRo, antiLa, antiADN y antiRNP y positivo débil el FAN (AU)

Uso de la inmunoglobulina intravenosa (IVIg) como terapia de rescate de rechazos refractarios en pacientes trasplantados renales / Use of intravenous immunoglobulin as rescue therapy of refractory Graft rejection in renal transplanted patients

La inmunoglobulina intravenosa (IVIg) ha sido utilizada en el pasado en pacientes con enfermedades autoinmunes, y también ha sido recientemente usada en pacientes sensibilizados que se encuentran en lista de espera para transpalnte renal, con el fin de reducir sus niveles de anticuerpos reactivos contra panel (PRA). Basados en estos reportes, se ha postulado también que la IVIg podría ser utilizada como un agente de rescate ene el tratamiento de rechazos refractarios en el transplante renal. Este trabajo reporta a cuatro pacientes, quienes se encontraban cursando su primer transplante renal. Tres de ellos habían sido trasplantados con donante vivo, dos relacionados y uno no relaiconado (esposo), y el cuarto había recibido un riñón cadavérico. El diagnóstico de rechazo, fue efectuado por biopsia renal y punción aspirativa renal. Inicialmente a todos los pacientes se les suministró esteroides y luego terapia antilinfocitaria, tres de ellos con anticuerpos monoclonales (OKT3), y el rescate con globulina antilinfocitaria (GAL). Luego del fracaso de la terapia antilinfocitaria, IVIg fue administrada a dosis de 500 mg/Kg/d durante siete días consecutivos. todos los rechazos fueron exitosamente revertidos. el mecanismo de acción de la IVIg puede estar relacionada con los anticuerpos antiidiotípicos. IVIg aparece como una alternativa útil para el rescate de receptores de transplantes renales con rechazos refractarios.

Uso de la inmunoglobulina intravenosa (IVIg) como terapia de rescate de rechazos refractarios en pacientes trasplantados renales / Use of intravenous immunoglobulin as rescue therapy of refractory Graft rejection in renal transplanted patients

La inmunoglobulina intravenosa (IVIg) ha sido utilizada en el pasado en pacientes con enfermedades autoinmunes, y también ha sido recientemente usada en pacientes sensibilizados que se encuentran en lista de espera para transpalnte renal, con el fin de reducir sus niveles de anticuerpos reactivos contra panel (PRA). Basados en estos reportes, se ha postulado también que la IVIg podría ser utilizada como un agente de rescate ene el tratamiento de rechazos refractarios en el transplante renal. Este trabajo reporta a cuatro pacientes, quienes se encontraban cursando su primer transplante renal. Tres de ellos habían sido trasplantados con donante vivo, dos relacionados y uno no relaiconado (esposo), y el cuarto había recibido un riñón cadavérico. El diagnóstico de rechazo, fue efectuado por biopsia renal y punción aspirativa renal. Inicialmente a todos los pacientes se les suministró esteroides y luego terapia antilinfocitaria, tres de ellos con anticuerpos monoclonales (OKT3), y el rescate con globulina antilinfocitaria (GAL). Luego del fracaso de la terapia antilinfocitaria, IVIg fue administrada a dosis de 500 mg/Kg/d durante siete días consecutivos. todos los rechazos fueron exitosamente revertidos. el mecanismo de acción de la IVIg puede estar relacionada con los anticuerpos antiidiotípicos. IVIg aparece como una alternativa útil para el rescate de receptores de transplantes renales con rechazos refractarios. (AU)

Tumor mucinoso del ovario con carcinoide mucinoso / Mucinous tumor of the ovary with mucinous cardinoid

Se presenta un caso de tumor mucinoso con zonas de adenocarcinoma mucinoso del ovario en una mujer de 29 años, con un nódulo tumoral sólido de 7x6x4 cm, que histológicamente correspondió a un carcinoide mucinoso, con frecuentes células argirófilas, positivas para cromogranina y otras con moco PAS positivo. Mediante inmunomarcación se detectó presencia de células positivas para ACTH y calcitonina. El carcinoide mucinoso es la variante menos frecuente del carcinoide del ovario y si bien los casos comunicados son muy pocos, parece comportarse agresivamente, de allí la importancia de su reconocimiento adecuado.